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Global microRNA expression profiling reveals differential expression of target genes in 6-hydroxydopamine-injured
Li Li1, Hui-Zhen Chen, Fang-Fang Chen
1Department of Human Anatomy and Neurobiology, Xuzhou Medical College, Tongshan Road 209#, Xuzhou, 221009, China.
Abstract:
Recent evidence indicates that microRNAs (miRNAs) play a key role in neurodegenerative diseases. However, little is known about how these small RNAs contribute to dopaminergic neuronal apoptosis. Here, we profiled the expression of miRNAs in MN9D cells with and without 6-hydroxydopamine (6-OHDA) treatment by miRCURY™ LNA microRNA arrays. We identified six miRNAs (miR-668-3p, let-7d-3p, miR-3077-3p, miR-665-5p, miR-99b-3p, and miR-323-3p) that were significantly lower and five miRNAs (miR-875, miR-207, miR-425-5p, miR-19b-3p, and miR-338-3p) that were significantly higher after 6-OHDA treatment. Among them, five have been demonstrated to be implicated in neurodegenerative diseases. Consistent with our prediction, the deregulated miRNA's target mRNAs, such as peroxiredoxin III (Prx III) and Myc, also showed changes in their expression levels. Furthermore, using a dual-luciferase reporter assay, we confirmed that Prx III was a direct target gene of miR-875. Taken together, these findings demonstrate that changes in miRNA expression occur after 6-OHDA treatment and suggest that miRNAs and their predicted targets have a potential role in apoptosis of MN9D cells.
Insights
MicroRNAs (miRNAs) are implicated in neurodegenerative diseases. This study reveals altered miRNA expression in dopaminergic cells after 6-hydroxydopamine (6-OHDA) treatment, suggesting a role in neuronal apoptosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their role in neurodegenerative diseases.
- The specific mechanisms by which miRNAs contribute to dopaminergic neuronal apoptosis remain largely unknown.
Purpose of the Study:
- To profile miRNA expression in MN9D cells following 6-hydroxydopamine (6-OHDA) treatment.
- To identify specific miRNAs and their target genes involved in 6-OHDA-induced dopaminergic neuronal apoptosis.
Main Methods:
- miRNA expression profiling using miRCURY™ LNA microRNA arrays.
- Analysis of target messenger RNA (mRNA) expression levels.
- Validation of miRNA-target interaction using a dual-luciferase reporter assay.
Main Results:
- Six miRNAs showed significantly decreased expression, and five showed significantly increased expression after 6-OHDA treatment.
- Expression levels of predicted target mRNAs, including peroxiredoxin III (Prx III) and Myc, were altered.
- Peroxiredoxin III (Prx III) was confirmed as a direct target gene of miR-875.
Conclusions:
- 6-hydroxydopamine (6-OHDA) treatment induces significant changes in miRNA expression in MN9D cells.
- Deregulation of specific miRNAs and their target genes may play a critical role in dopaminergic neuronal apoptosis.
- These findings highlight potential miRNA-based therapeutic targets for neurodegenerative diseases.
